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PubMed2005

Stem cell factor modulates the expression of steroidogenesis related proteins and FSHR during ovarian follicular development.

Stem cell factor (SCF) is essential for the development of primordial follicles. By using cultured ovaries from neonatal rats, the effect of SCF on early follicular development was investigated. Steroidogenesis is a hallmark of follicular development. Expressions of three key protein factors in steroidogenesis, SF-1, StAR, and P450arom, were investigated using immunohistochemistry and in situ hybridization. SF-1 and StAR proteins were expressed in all ovarian cells. P450arom mRNA was localized exclusively in oocytes implying that estrogen might be synthesized by oocytes at this stage. SCF up-regulated the mRNA and protein expression of these proteins, suggesting SCF might promote the production of estrogen during this period of time. To study the differentiation status of follicular cells, the expression of FSHR and its response to SCF treatment was examined by using semi-quantitative RT-PCR. The results showed that SCF inhibited the expression of FSHR mRNA. It was also observed that SCF stimulated the expression of basic fibroblast growth factor (bFGF) in oocytes. Inactivation of bFGF by its neutralizing antibody resulted in a reversal of the inhibitory effect of SCF on the expression of FSHR. Therefore, the FSHR inhibitory effect of SCF could be mediated by bFGF. In summary, it seems that, at the early stages of follicular development, SCF might stimulate oocytes to produce estrogen while it inhibits the differentiation of granulosa cells that are the major sources of estrogen at the late stages of follicular development.

Animals↗
PubMed1990

Effect of timing of prostaglandin PGF 2 alpha injection subsequent to embryo collection on the resumption of normal follicular development following superovulatory treatment in cattle.

Nonlactating Holstein and Jersey cows (n = 24) were superovulated and ovarian follicular development was monitored by transrectal ultrasound during the period after embryo recovery. Luteolysis was induced by two injections of prostaglandin F(2)alpha (PGF; 25 mg Lutalyse; 12-h interval) at specific times after superovulatory induced estrus (Treatment 1, Day 9; Treatment 2, Day 12; Treatment 3, Day 17; Treatment 4, Day 25; superovulatory estrus = Day 0 of Cycle 1). Follicular development was monitored during Cycle 1 before and after PGF injection and continued through the ensuing estrous cycle (Cycle 2). Superovulation led to more than one embryo collected in 14 cows (mean = 8.71 embryos: positive superovulatory response [PSR] cows), while 10 cows were not successfully superovulated (mean = 0.1 embryo; negative superovulatory response [NSR] cows). These cows differed in terms of number of unovulated follicles detected at embryo collection (4.21 vs 17.2, PSR vs NSR) and plasma progesterone during the superovulatory estrous cycle (32.3 ng/ml PSR vs 8.6 ng/ml NSR). Follicular development during Cycle 1 started sooner in NSR than in PSR cows (day by class by response P<0.03) and was initiated on Days 11 to 12 in NSR cows and on Days 19 to 20 in PSR cows. Interval to estrus after PGF averaged 6.3 d. Cows having short intervals to estrus had follicles at the time of PGF injection. Treatment influenced the length of Cycle 1, but it did not affect the interval to estrus after PGF, the length of Cycle 2, or follicular development during Cycle 2. The results indicate that 1) the timing of PGF injection after embryo collection does not influence subsequent follicular populations, 2) elongated estrous cycles and intervals to estrus after PGF in superovulated cattle are a function of decreased follicular activity, and 3) the presence of numerous corpora lutea and not the superovulatory treatment, per se, seem to attenuate follicular growth.

Journal Article↗
PubMed2000

A model of follicular development and ovulation in sheep and cattle.

A dynamic model to describe ovarian follicular development following commitment has been developed. It identifies follicular growth with oestradiol production and assumes that this growth is the result of intra-ovarian stimulation, gonadotrophin stimulation, and inhibitory interactions among the follicles, where larger follicles suppress the growth of the smaller follicles. The variables of the model are the levels of oestradiol in each follicle at commitment, the rate of change of oestradiol production by individual follicles during follicular development, and the level of oestradiol that will induce luteinizing hormone (LH) surge. Changes in the variables of the model could be associated with both genetic and environmental effects. The behaviour of the model is consistent with experimental observations. The model can be expanded to include exogenous follicle-stimulating hormone (FSH) administration assuming that FSH is associated with advancing the maturation of gonadotrophin-dependent follicles without affecting the number of committed follicles. The use of the model to explore FSH administration strategies is demonstrated. The model confirms that the response to FSH administration depends on both the amount of FSH and the time of administration. The largest number of double ovulations occurred when FSH was given at the time of the deviation of the dominant and subordinate follicles.

Animals↗
PubMed1994

Follicular development and superovulation response in cows administered multiple FSH injections early in the estrous cycle.

To determine whether follicular development, superovulation and embryo production were affected by the absence or presence of a dominant follicle, cows were administered injections of FSH twice daily in the early (Days 2 to 6, estrus=Day 0) or middle stage (beginning on Day 10 or 11) of the estrous cycle. Treatment with FSH early in the cycle stimulated follicular development in 83 to 100% of all cows from 4 groups evaluated at different times after PGF2alpha treatment on Days 6 and 7. However, the proportion of cows with >2 ovulations varied from 31 to 62.5%, indicating that induction of follicular development may occur in the absence of superovulation. When compared with cows treated in the middle of the cycle, no differences were observed in the proportion of cows with >2 ovulations (31 vs 20%), ovulation rate. (26.0+/-6.3 vs 49.6+/-25.8), production of ova/embryos (13.3+/-3.2 vs 14.4+/-3.4), or the number of transferable embryos (8.0+/-3.6 vs 5.4+/-1.5; early vs middle, respectively). The proportion of the total number of embryos collected that were suitable for transfer was greater (P<0.01) in cows treated early in the cycle (60%) than at midcycle (37.5%). The diameter of the largest follicle observed by ultra-sound prior to initiation of FSH treatment in the early stage of the cycle (10.0+/-2.0 mm) was smaller (P<0.05) than at midcycle (16.8+/-1.3 mm). These results demonstrate that superinduction of follicular development is highly consistent after FSH treatment at Days 2 to 6 of the cycle and that superovulation and embryo production are not less variable than when FSH is administered during the middle of the cycle. However, superovulation in the early stage of the cycle may increase the proportion of embryos suitable for transfer.

Journal Article↗
PubMed1984

Effect of enucleation of the corpus luteum at different stages of the luteal phase of the human menstrual cycle on subsequent follicular development.

To investigate the mechanism of suppression of follicular development during the luteal phase of the human menstrual cycle, the corpus luteum was enucleated surgically from 10 women at various times after ovulation. In the 24 h after CL enucleation there was an immediate and rapid fall in the concentration of oestradiol and progesterone and a temporary decline in the concentration of FSH and LH. Within 3 days, however, all 10 women showed evidence of renewed follicular activity as indicated by a progressive rise in the concentration of oestradiol. This rise was preceded by a rise in the concentration of FSH and LH, and ovulation, as indicated by a mid-cycle surge in LH and rise in the concentration of plasma progesterone, occurred 16-19 days after enucleation. There was no significant difference in the time to ovulation following enucleation at different times of the luteal phase. The post-operative follicular phase, measured from the time of enucleation, was 3 days longer than that observed pre-operatively from the first day of menstrual bleeding. In the follicular phase of post-operative cycles the concentration of FSH was higher and that of oestradiol lower than the corresponding values before surgery. These results indicate that the absence of healthy antral follicles in the luteal phase of the cycle is due to the inhibitory effects of the corpus luteum. The fact that, after CL enucleation, emergence of the dominant follicle was always preceded by a rise in the concentration of FSH and LH suggests that suppression of gonadotrophins by ovarian steroids secreted by the corpus luteum is responsible for the inhibition of follicular development during the luteal phase of the cycle.

Adult↗
PubMed2006

Comparison of the effect of estradiol benzoate plus progesterone and GnRH on the follicular wave emergence and subsequent follicular development in CIDR-treated, lactating dairy cows with follicular cysts.

This study examined the effect of estradiol benzoate (EB) plus progesterone (P4) as compared with GnRH on follicular wave emergence and follicular development, and synchrony of ovulation and pregnancy rates following a second injection of GnRH in a controlled internal drug release (CIDR)-based timed AI (TAI) protocol in lactating dairy cows with follicular cysts. Lactating dairy cows diagnosed with follicular cysts received a CIDR device, with an injection of 2mg EB plus 50mg P4 (EB+P4 group) or with an injection of 100 microg GnRH (GnRH group) at the beginning of the experiment (day 0). Thereafter, all received PGF(2alpha) at the time of CIDR removal on day 7, GnRH on day 9, and TAI 16 h later. Follicular wave emergence occurred within 7 days in 12/15 EB plus P4-treated and 14/15 GnRH-treated cows (P>0.05). The interval to wave emergence was longer in the EB+P4 group (4.8+/-0.4 days) than in the GnRH group (2.0+/-0.2 days). The mean diameters of preovulatory follicles and the proportion of cows with preovulatory follicles greater than 12 mm on day 9 did not differ between groups (P>0.05). The proportion of cows with synchronized ovulations by 40 h after the GnRH injection on day 11 and pregnancy rates to TAI did not differ between the EB+P4 (13/15 and 36.7%) and the GnRH (14/15 and 53.3%) groups, respectively. Results suggest that a single treatment with EB plus P4 as compared with GnRH simultaneously with CIDR insertion in lactating dairy cows with follicular cysts will result in relatively asynchronous emergence of a new follicular wave, but subsequently similar sizes of preovulatory follicles and synchronous ovulation, resulting in similar pregnancy rates to TAI.

Animals↗
PubMedDate not supplied

Mammalian follicular development and atresia: role of apoptosis.

The regulation of follicular development and atresia is a complex process and involves interactions between endocrine factors (gonadotropins) and intraovarian regulators (sex steroids, growth factors and cytokines) in the control of follicular cell fate (i.e. proliferation, differentiation and programmed cell death). Granulosa and theca cells are key players in this fascinating process. As atresia is the fate of most follicles, understanding of how these physiological regulators participate in determining the destiny of the follicle (to degenerate or to ovulate) at cellular and subcellular levels is fundamental. This short review summarizes the role of intraovarian modulators of programmed cell death in the induction of atresia during follicular development.

Animals↗
PubMed1975

Studies of oogenesis and follicular development in the golden hamster. 3. The initiation of follicular growth in vitro.

Ovaries derived from hamsters on day 5 p.p. were maintained in organ culture for 15 days. It was found that the process of follicular growth was severely retarded in organ cultures devoid of gonadotrophic hormones. The addition of FSH and LH resulted in a partial improvement in follicular development, a result which supports the view that gonadotrophic hormones are important in the early development of the ovary.

Animals↗
PubMed2003

Involvement of angiopoietin-tie system in bovine follicular development and atresia: messenger RNA expression in theca interna and effect on steroid secretion.

Angiogenesis is involved in the local mechanisms that regulate follicular development and ovulation. Recently, the angiopoietin (ANPT)-Tie system has been shown to be required to regulate angiogenesis and blood vessel regression. Expression of the ANPT-Tie system in the cyclic ovary suggests that the relative changes in the expression of ANPT-1 and ANPT-2 influence the stability of ovarian blood vessels. In this study, we investigated 1) the mRNA expression for ANPT-1, ANPT-2, and endothelial cell-specific receptors Tie1 and Tie2 in the theca interna (TI) of the bovine developing, mature, and atretic follicles by using a semiquantitative reverse transcription polymerase chain reaction assay and 2) the effect of ANPT on the secretion of steroid hormones from bovine preovulatory follicles in vitro using a microdialysis system (MDS) implanted in the thecal layer. Bovine follicles were classified as developing, mature, and atretic according to size, follicular fluid content of estradiol (E2) and progesterone (P4), and characteristics of granulosa cells (GCs). Both ANPT and Tie mRNA were expressed in the TI, whereas GCs expressed ANPT mRNA only. The expression of ANPT-2 mRNA was decreased in the mature follicles. This decrease resulted in a decrease in the ANPT-2:ANPT-1 ratio (an index of instability of blood vessels), indicating that the blood vessels became more stable or mature. The early atretic follicles showed a higher ANPT-2:ANPT-1 ratio and higher Tie2 mRNA expression than did other follicles at healthy or later atretic stages. This finding may imply that blood vessels become unstable at the initial stage of follicular atresia. In both mid and late atretic follicles, Tie2 mRNA expression dramatically decreased, indicating a disruption of the ANPT-Tie system. In the MDS experiment, an infusion of ANPT-1 or ANPT-2 increased P4 release, whereas both ANPTs inhibited the release of androstenedione. ANPT-1 also increased E2 release. These results showed that the mRNA expression for ANPT-1, ANPT-2, Tie1, and Tie2 changes during follicular development, maturation, and atresia in bovine follicles and that ANPTs affect steroidogenesis in the preovulatory follicle. The results suggest that the ANPT-Tie system is involved the structural (angiogenesis) and secretory changes that occur during follicular development and atresia.

Angiopoietin-1↗
PubMed2002

Potential role of activin A in follicular development during the second half of pregnancy in the golden hamster: utero-placental source of activin A.

Numerous antral follicles develop during the second half of pregnancy in the golden hamster. However, mechanisms regulating follicular development during this period are unknown. Because inhibin and activin are related to follicular development, these hormones were studied to gain insight into any potential roles in follicular development. Plasma inhibin A and B suddenly increased from day 8 of pregnancy, reached peak levels on day 10 and gradually declined to term. Plasma activin A gradually increased from day 8 to day 15 of pregnancy, and this was followed by an abrupt decrease at day one of lactation. Ovariectomy on day 12 of pregnancy rapidly reduced plasma inhibin A and B, but not activin A levels. Hysterectomy or placentectomy on day 12 of pregnancy caused an abrupt decrease in the levels of plasma activin A and FSH, but not inhibin A and B at 6 h after surgery. Hysterectomy also induced atresia of large antral follicles at 24 h after surgery. These results indicate that antral follicles are the main source of circulating inhibin A and B, whereas uteri and placentae are the main source of circulating activin A. These results suggest that increased levels of activin A may be involved in folliculogenesis in the ovary during the second half of pregnancy in the golden hamster.

Activins↗
PubMed1981

[Effect of copulation on the follicular development and ovulation in rat (author's transl)].

The follicular development, ovulation and position of the oocytes in the stretched tubes at different phases and times of the rat's ovarian cycle, and the effect of different conditions of copulation on these processes have been studied. With copulation from the 16th hour of diestrus to the 16th hour of proestrus, the number of large follicles, follicles total, and oocytes plus follicles increased significantly. With copulation from the 10th hour of proestrus to the 10th hour of estrus, the number of oocytes, small follicles and follicles total increased significantly. Copulation, therefore, facilitates the processes of follicular development and ovulation.

Animals↗
PubMed2004

Expression of mitochondria-dependent apoptosis genes (p53, Bax, and Bcl-2) in rat granulosa cells during follicular development.

OBJECTIVE: We examined rat ovarian granulosa cells at different follicular stages and evaluated the apoptosis pattern of the mitochondria-dependent genes during folliculogenesis. METHODS: After down-regulating ovarian function with gonadotropin-releasing hormone agonist (GnRHa), granulosa cells were collected from the rat ovary at different stages of the following different hormonal treatment paradigms: stage E (after estrogen treatment), EF (after E + follicle-stimulating hormone [FSH] treatment), and EF hCG (after E + FSH + human chorionic gonadotropin treatment). To evaluate the in vitro susceptibility of granulosa cells at different developmental stages to apoptosis, the collected cells were cultured in a serum-free medium with or without E2 for 24 hours. The regulation of apoptosis in the granulosa cells was analyzed using fluorescein-activated cell sorting, quantitative competitive polymerase chain reaction, and western blot methods. RESULTS: The apoptosis rate of the freshly isolated granulosa cells tended to increase according to the hormonal treatment paradigm. In addition, during the hormone treatment, mitochondria-dependent apoptosis genes showed the following changes: although the Bax mRNA level did not change, the Bcl-2 mRNA level decreased significantly (P <.05). The p53 mRNA level increased significantly (P <.05) and closely matched the apoptosis rate (R = 0.7, P <.05). The expression of the active form of the caspase-3 protein (the final executioner of cell death) tended to increase and showed a good correlation with the apoptosis rate (R = 0.96, P <.01). After an in vitro culture of the granulosa cells, the apoptosis rate tended to increase at all stages, particularly stage EF hCG (P <.05). Bax and p53 mRNA tended to increase and showed a good correlation with the apoptosis rate (R = 0.64, P <.05 and 0.86, P <.01). The Bcl-2 mRNA level tended to decrease at all stages showing no correlation with the apoptosis rate. The expression level of the active caspase-3 protein tended to increase at all stages and showed a good correlation with the apoptosis rate (R = 0.93, P <.01). CONCLUSION: Apoptosis of rat ovarian granulosa cells tends to increase according to the stage of follicular development. Among the mitochondria-dependent genes, p53 closely correlates with granulosa cell apoptosis during follicular development.

Animals↗
PubMed2004

Ovarian follicular development is initiated during the hormone-free interval of oral contraceptive use.

We evaluated ovarian follicular development in women during compliant use of oral contraceptives (OC). Thirty-six healthy women received: [35 microg ethinyl estradiol (21)/180 microg norgestimate (7), 215 microg norgestimate (7), 250 microg norgestimate (7)]; [30 microg ethinyl estradiol (21)/150 microg desogestrel (21)]; or [20 microg ethinyl estradiol (21)/100 microg levonorgestrel (21)] for 3 consecutive 28-day cycles. Transvaginal ultrasonography was performed every third day to monitor follicular development. If a follicle reached > or = 14 mm, ultrasonography was performed daily and blood drawn every other day to determine estradiol-17beta concentrations. Seventeen of 36 women (47%) grew follicles > or = 10 mm. Nine of the 17 women (53%) grew follicles > or = 14 mm, in association with increased serum concentrations of estradiol-17beta. Thirty-seven of 43 follicles > or = 10 mm (86%) emerged during the hormone-free interval (HFI). No ovulations were observed. Our results supported the hypothesis that follicular development to an ostensibly ovulatory diameter occurs during compliant OC use, in association with loss of endocrine suppression during the HFI.

Adolescent↗
PubMed2004

Effects of GnRH antagonist treatment on follicular development and angiogenesis in the primate ovary.

Angiogenesis is required for normal follicular development but the role of gonadotrophins in the control of follicular angiogenesis remains to be elucidated. This study investigated the effects of treatment with GnRH antagonist in vivo on follicular development and angiogenesis in the marmoset. GnRH antagonist was administered on either follicular day 0 or day 5 of the 10-day follicular phase with ovaries collected on day 10. Ovaries from control marmosets were studied at day 5 (mid follicular phase) and day 10 (periovulatory period). Ovaries were fixed, serial sectioned and subjected to morphological analysis and immunocytochemistry to determine cell proliferation and follicular endothelial cell area and in situ hybridization to assess changes in expression of vascular endothelial growth factor (VEGF). Treatment with GnRH antagonist from day 0-10 resulted in an absence of dominant preovulatory follicles seen in controls. In the remaining tertiary follicles granulosa, theca and endothelial cell proliferation was reduced, resulting in a minor reduction in vascular density. However, VEGF mRNA expression was unaffected by treatment. Treatment from day 5-10 did not prevent development of ovulatory size follicles, but they were atretic and lacked VEGF mRNA. These results suggest that while VEGF expression in the preovulatory follicle is under gonadotrophic control it is not dependent on normal gonadotrophin secretion in tertiary follicles, indicating that there are other paracrine factors regulating VEGF expression in the developing ovarian follicle.

Animals↗
PubMed1996

Incongruent follicular development reduces gamete intrafallopian transfer pregnancy rate.

OBJECTIVE: To test the null hypothesis that asymmetric or incongruent follicular development does not influence GIFT pregnancy rates (PRs). DESIGN: A prospective comparative study. SETTING: Tertiary referral center for infertility. PATIENT(S): Ninety-three consecutive infertile patients having GIFT. INTERVENTION(S): Controlled ovarian hyperstimulation and GIFT. MAIN OUTCOME MEASURE(S): The incongruity ratio as a parameter of the asymmetry in follicular development and the clinical PR. RESULT(S): An inverse relationship was observed between the degree of incongruity and the clinical PRs. In patients with an incongruity ratio < 1.5, the clinical PR was 56.1%. In patients with an incongruity ratio > or = 1.5, the clinical PR was only 17.3%. CONCLUSION(S): Incongruent follicular development during controlled ovarian hyperstimulation has a marked negative influence on the outcome of GIFT cycles. Factors such as side of the gamete transfer and oocyte quality did not account for the observed differences.

Adult↗
PubMed1981

Ovarian morphology of the dusky leaf monkey (Presbytis obscura): follicular development and atresia.

The ovarian morphology and the pattern of follicular development and atresia have been described for the dusky leaf monkey, Presbytis obscura, on the basis of a study of material from 44 female monkeys collected at various stages of the menstrual cycle, pregnancy and lactation. Marked differences were found in the dimensions of many ovarian components between this monkey and the other species of langur previously described. During follicular development the oocyte increased in diameter from 28 micrometer in the primordial follicle to a maximum of 85 micrometer in a pre-ovulatory follicle measuring 8.0 x 4.0 x 7.0 mm. The majority of developing follicles, however, underwent atresia with the theca interna transforming into interstitial tissue. Although present in the follicular phase of the menstrual cycle, this tissue was most pronounced during early pregnancy, at a time when lutealisation also occurred, resulting in the formation of corpora lutea atretica. These findings have been discussed in relation to other catarrhine primates.

Animals↗
PubMed2004

Expression of mRNA for the angiopoietin-tie system in granulosa cells during follicular development in cows.

Recent findings indicate that the changing profile of angiopoietins (ANPT) and their receptor Tie2 are closely associated with development and regression of the vascular network in the cyclic ovary. We previously reported that mRNA expression for the ANPT-Tie system in theca interna changes during bovine follicular development and atresia, and both ANPTs affect steroidogenesis in the preovulatory follicle. The aim of this study was to investigate mRNA expression for ANPT1, ANPT-2 and Tie2 in granulosa cells (GC) during follicular development in the cow. Bovine follicles were classified according to the estradiol-17beta (E(2)) concentration in follicular fluid (FF) as follows: (1) E(2)<0.5, (2) 0.5 180 ng/ml FF. Semi-quantitative RT-PCR analysis revealed that the expression of ANPT-1 mRNA was not detected in most of the follicle with E(2)<5 ng/ml (diameter of 5-10 mm), but clearly detected in all follicles with E(2)>5 ng/ml (diameter of >10 mm). The mRNA expression for ANPT-2 was drastically decreased in the follicles with E(2)>5 ng/ml. Tie2 mRNA expression remained unchanged at the different stages of follicular development. The present data show that ANPT-1 becomes predominant in the follicle producing high levels of E(2), indicating the possible switch-over from ANPT-2 (antagonist) to ANPT-1 (agonist). Thus, the result suggests that the ANPT-Tie system in bovine GC may stimulate E(2) secretion rather than angiogenesis in the late stages of follicular development.

Angiopoietin-1↗
PubMed1977

An autoradiographic study of long-term follicular development in the cyclic hamster.

The time required for ovarian follicular development in the cyclic hamster was determined by marking follicles with [3H]-thymidine on day 1 of the estrous cycle (day of ovulation) and by following their fate over the next three cycles by autoradiography. A model of follicular development was formulated, based on the total number of follicles and the changing percentage of labelled follicles with time. It was estimated that 20 days elapsed before a preantral follicle with two to three layers of granulosa cells (stage 1) was able to ovulate. Follicles spent eight days in stage 1 and an additional eight days in stage 2 (4-5 granulosa layers). Preantral follicles entering stage 3 (6-7 granulosa layers) and 4 (greater than 8 layers) on day 1 of the cycle ovulated four days later. Approximately 30 follicles per ovary entered and left stage 1 each cycle, representing a 50% turnover. Of the follicles leaving stage 1, about 50% were transformed into stage 2 follicles; the remaining ones underwent atresia. Stage 2 follicles also had a 50% turnover each cycle. Half of the stage 2 follicles underwent atresia; the remainder developed into stages 3 and 4 follicles. Fifty percent of the stages 3 and 4 follicles present on day 1 of the cycle ovulated at the next estrus with the remainder undergoing atresia.

Animals↗